Alfuzosin hydrochloride has the chemical name N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide hydrochloride and has the structural formula as Formula I.

Alfuzosin hydrochloride is an antagonist of the α-adrenergic receptor, and is useful as an antihypertensive agent and dysuria treatment agent.
The earliest known synthesis of alfuzosin hydrochloride, by Manoury et al, is described in U.S. Pat. No. 4,315,007. The synthetic method employed is depicted in the following reaction scheme 1.

The patent 007' teaches the preparation of alfuzosin or a salt thereof by reacting 4-amino-2-chloro-6,7-dimethoxy quinazoline of formula (II) with 3-methylaminopropionitrile of formula (III) in the presence of isoamyl alcohol to obtain N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine of formula (IV) which is further hydrogenated in the presence of Raney-Nickel using 15% ammoniacal ethanol by applying 80 Kg pressure at 70° C. for 96 hours to obtain N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine of formula (V) which is then converted to the hydrochloride salt. The obtained N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine hydrochloride is then treated with carbonyldiimidazole-activated tetrahydrofuroic acid by adding a diamine compound in the presence of carbonyldiimidazole to obtain alfuzosin base which is then converted into alfuzosin hydrochloride salt.
The process has many disadvantages, for example:
a) The use of isoamyl alcohol as a reaction solvent is irritating to the skin, eyes and respiratory system. Also, it results in an extended reaction time consequently leading to formation of 10-12% of one of the potential impurities termed herein as “alfuzosin impurity A”

This impurity carries over to the subsequent steps for preparing alfuzosin, making it more difficult to isolate a pure product, hence the process is not viable industrially.
b) The use of the high pressure of 80 kg/cm2 and dry conditions for a long duration in the hydrogenation, makes the process unsuitable for industrial scale up. The yield and the purity of the end product obtained by using the stated procedure in accordance with scheme I is therefore greatly compromised. This leads to an overall increase in the handling and production costs.
A refinement of the above process is described in US2007/0105880 (“'880”). Nevertheless, the process of '880 suffers from several significant drawbacks. For example, the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine of formula (IV) is hydrogenated at a high pressure of 10-15 kg using ammoniacal ispropanol solution. This reaction is carried out under dry conditions. Under the reaction conditions described in '880, the compound N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine of formula (V) does not precipitate out; a seed is required to precipitate compound (V), which makes the process cumbersome and non-reproducible. Further, '880 claims the use of a base for preparation of N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine of formula (IV). However, there is no example disclosing the use of any base in the reaction.
The alfuzosin obtained in the next step on '880 by reaction of the compound of formula (V) with carbonyldiimidazole-activated tetrahydrofuroic acid, is impure in nature and hence needs repetitive crystallization before converting it into the hydrochloride salt.
Processes for the preparation of alfuzosin and its pharmaceutically acceptable salts have also been described in U.S. Pat. No. 5,545,738, GB Patent No. 2231571, and US2007/0066824. U.S. Pat. No. 5,545,738 discloses a process for preparing the dihydrate form of alfuzosin hydrochloride. GB 2231571 discloses a process for preparing alfuzosin or salts thereof comprising reacting an isothiourea derivative with an amine and cyclising the resulting product to form alfuzosin. US2007/0066824 discloses a process for preparing salts of alfuzosin comprising a) esterifying tetrahydrofuroic acid; b) condensing the esterified product of step a) with 3-methyl amino propylene diamine to get N1-methyl-N2-tetrahydrofuroyl propylene diamine; c) condensing N1-methyl-N2-tetrahydrofuroyl propylene diamine with 4-amino-2-chloro-6,7-dimethoxyquinozoline to yield alfuzosin free base; d) treatment of alfuzosin free base of with a pharmaceutically acceptable acid to afford a pharmaceutically acceptable acid addition salt of alfuzosin.
The processes described in the above patents involve multiple steps and involve the formation of an unstable ester as an intermediate, which leads to decreased yield and purity of the product.
Therefore, there exists a need for a more economical and efficient method of making alfuzosin which is suitable for industrial scale up.
The present invention provides an improved process for synthesis of alfuzosin which avoids all the disadvantages associated with the prior art processes.